Growth, development and regeneration of three types of fetal mouse neurons will be studied in vitro in relation to mechanisms underlying the formation of regionally organized synaptic networks in specific CNS target tissues: 1. dorsal root ganglion (DRG) cells cocultured with dorsal-horn regions of spinal cord or dorsal-column nuclei of medulla; 2. retinal ganglion cells cocultures with superior colliculus explants; 3. monoaminergic brainstem neurons (locus coeruleus and raphe) cocultured with explants of hippocampus or cerebral neocortex. In some of these studies, suspesnsions ofdissociated CNS target neurons will be introduced into previously established cultures or organized explants. DRG, retinal and aminergic neurons will also be cocultured with carefully positioned pairs of well-defined target and non-target CNS tissues, in extension of our competition experiments with separate explants of dorsal and ventral cord presented to isolated DRGs. Coordinated electrophysiologic, pharmacologic, and cytologic analyses will be carried out during development of these three types of cocultures to study mechanisms involved in: 1. preferential growth of DRG, retinal, and aminergic neurities in relation to rarget and non-target tissues; 2. formation of specific functional synaptic connections with CNS target neurons; 3. positional and phenotypic specificity properties which may be encoded in these arrays of cocultured neurons; 4. possible growth regulatory systemsin these three types of neurons leading to sequential correction of nonselective neuritic arborizations and transient synaptic connections which may develop initially follwong experimentally controlled contacts with both target and non-target CNS tissues. The developmental studies in cocultures of fetal tissues will be extended to problems in CNS regeneration by: 1. delayed presentation of fetal tissue until the DRG, retinal and monoaminergic neurons have matured for several weeks in culture, or vice versa; 2. selective microsurgical lesions after maturation in coculture to permit studiesof the relative capacity for regeneration of specific connections.